Meet the Nobels: Golgi and Cajal

Camillo Golgi (1843–1926)

Camillo Golgi was born in Corteno (Italy) in 1843. Encouraged by his father, a physician, Golgi attended the medical school at the University of Pavia, where he graduated in 1865. In search of the right direction to steer his own career, Golgi came across two great mentors, Cesare Lombroso and Giulio Bizzozero, who instilled in him a major interest for the nervous system and histology, respectively. At that time, the reticular theory postulated by Gerlach in 1871 was ruling the roost. According to this doctrine, the nervous system was formed by a continuous syncytium of cells, a protoplasmic network made of dense filaments from which the nerve fibers were originating. It was 1873 when Golgi, constrained in a makeshift laboratory in the kitchen of a small flat, started playing with potassium dichromate and silver nitrate, and formulated the recipe for the famous “reazione nera” (black reaction). For the first time, cells of the nervous system could be stained black, to appear as single entities against a light, clear background. The new staining was screaming for a different, new reality (the nervous system being composed by single cells) which Golgi managed to catch only in part.

Golgi probably could not imagine, but the era of modern neuroanatomy had just begun in that kitchen!

Less is more

One major benefit of Golgi’s staining was its “poor performance”. Indeed, only a small proportion (1-5%) of the cells turned visible upon the silver impregnation, and these cells were stained in their entirety. Golgi decided to report on paper what he could see through his microscope: by using a camera lucida, he faithfully drew the neurons and all their ramifications, tracing as many details as possible. Without this mysterious selectivity, it would have been impossible for Golgi or anybody else to discern one cell from another.

While defending the reticular theory, Golgi suggested that the protoplasmic protrusions (now identified as dendrites) had only a nutritive function, as suggested by their close association with blood vessels. Instead, the cylinder axis (now identified as the axon) was responsible for forming the diffuse nervous network [1]. Sadly, Golgi was wrong; the key to unlock the real essence of the nervous system was there, but he just missed it.

Santiago Ramon y Cajal (1853-1934)

Santiago Ramon y Cajal was born in Petilla de Aragon (Spain) in 1853. Differently from Golgi, Cajal was not a behaving student and his turbulent personality created more than a few problems for his father, a surgeon and Professor of Applied Anatomy who struggled to impose some discipline on his son. Clashing with his father’s wishful thinking, young Cajal showed a strong propensity for arts, a sibylline skill that proved critical later in his career as a scientist. Despite these initial issues, Cajal managed to graduate from the medical school at the University of Zaragoza (Spain) in 1873, and then obtain a a doctorate in medicine in 1877, after a few months spent at the front. But it was only in 1887 that Cajal learned about the Golgi staining, thanks to some preparations shown to him by Professor Luis Simarro. Cajal thought out of the box and immediately perceived the potential of the staining. He worked hard to optimize the protocol and make it more predictable. Two expedients in particular allowed him to master the new technique: the younger, even embryonic, stage of neurons (before the myelination process was completed) and the thinner sectioning of his preparations.

The father of neuroscience

It was by using his modified version of the Golgi staining and his artistic talent that Cajal could obtain some of the most evocative images ever seen, which allowed him to formulate the “neuron doctrine” and become the undisputable “father of neuroscience”. According to Cajal, in fact, the nervous system, just like any other tissue, was composed of single, independent cells, communicating in a contiguous, rather than continuous, fashion. Cajal also introduced the concept of “dynamic polarization”, which he illustrated in his drawings with pointing arrows. According to this principle, the information flows in a specific direction: from the dendrites to the cell body and then to the axon, to finally reach the next cell [2].

This new paradigm created a huge discrepancy within the scientific community, initially torn between the two opposing theories. However, a meeting held in Berlin in 1889 (the German Anatomical Society Congress) moved the needle of the scale towards the pro-neuron party. On this occasion Cajal, very determined to impress the audience, brought with him some of his preparations and assertively exposed his new theory. The plan worked to perfection: Kolliker, a well-known histologist of the time, was among those present and was stunned by Cajal’s presentation. The “neuron theory” rapidly spread across Europe and became the fundamental dogma of neuroscience.

The Nobel Prize ceremony

By the time the Nobel Prize was awarded, in 1906, the “neuron theory” was well-consolidated and widely accepted. However, Golgi never admitted defeat, and kept defending his theory - now called “neo-reticular” - until the end. A lecture given in Stockholm was a lapse of style for the Italian, who, with a questionable speech entitled “The Neuron Doctrine - Theory and Fact”, shot a severe critique to Cajal’s dogma. The Spanish, however, put on a good face and the next day he simply gave his pre-established lecture, avoiding any further hostility.

Golgi and Cajal’s legacy

The contribution of Golgi and Cajal to neuroscience is tremendous. Even today, the details of their drawings witness the magnificence of their work and release a deep sense of admiration. But they did much more than this. Golgi in particular, spent part of his time studying the physiopathology of the kidney and the life cycle of the parasite responsible for malaria, leading to some important advancements. Golgi’s name is indissolubly linked to the intracellular organelle known as the Golgi apparatus, the Golgi tendon organs, the Muller-Golgi tubules, the Golgi-Mazzoni corpuscle and the two different types of neurons known as Golgi type I and Golgi type II.

Cajal’s attention, instead, remained mainly confined to the nervous system, where he contributed with his extraordinary long-term outlook in a multitude of ways. Indeed, not only did he formulate the neuron doctrine, but he also identified the growth cone as a specific element of the neuron and speculated that its development might have been regulated by morphogenic signals. Cajal also identified the presence of dendritic spines, which Golgi mistook for an artefact of his staining, and made some important advances in the study of the developing nervous system.

References

1. Mazzarello, P. (2018). From images to physiology: A strange paradox at the origin of modern neuroscience. Progress in Brain Research, 243, pp. 233-256. https://www.sciencedirect.com/...
2. De Carlos, J., Borrell, J. (2007). A historical reflection of the contributions of Cajal and Golgi to the foundations of neuroscience. Brain Research Reviews, 55(1), pp. 8-16. https://www.sciencedirect.com/...

About the Author

Elena received her PhD in Experimental Neuroscience at the San Raffaele Institute, Italy. She then moved to Cambridge (UK) for her postdoc and finally to Brighton (UK) to work as a lab technician. Her main interest has been focused on translational neuroscience, and she has been working with stem cells and animal models of neurodegenerative diseases, including multiple sclerosis and spinal cord injury.

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